We propose to investigate IgA proteases, microbial enzymes which have specificity in cleaving human serum and secretory IgA immunoglobulins. We plan to compare the specificity of IgA proteases from S. sanguis, N. gonorrhoeae, and N. meninggitidis and to study the influence of human intestinal fluid on IgA protease activity, including the effect of bile acids and natural inhibitors to the enzyme. A detailed study of the proteolytic fragments of IgA in the feces of normal persons and those with gastrointestinal disease will be undertaken, and the relationship of IgA protease to human blood group substances will be examined. The effect of IgA protease on the biologic properties of antibodies of both subclasses of human IgA in the secretory and serum system will be studied using isotopically labelled antibodies and hemagglutination techniques. We plan to employ a variety of immunologic techniques, plus techniques used for isolation and characterization of proteins and enzymes such as polyacrylamide gel electrophoresis, immunoelectrophoresis, double diffusion in agar gel, and separation of proteins by molecular seive chromatography, ion exchange chromatography, and isoelectric focusing.